Evidence map›Paper›PMID 40907495›Full record

ArticleCell reports. Medicine2025

Epigenetic modulation of BARD1 to enhance anti-VEGF therapy.

Emine Bayraktar, Cristian Rodriguez-Aguayo, Elaine Stur, Sudhir Kumar, Lingegowda S Mangala, Nicholas B Jennings, Nazende Nur Bayram, Sara Corvigno, Amma Asare, Cristina Ivan and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Emine BayraktarDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston, Houston, TX 77030, USA.
Cristian Rodriguez-AguayoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Elaine SturDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sudhir KumarDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Lingegowda S MangalaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nicholas B JenningsDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nazende Nur BayramDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sara CorvignoDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Amma AsareDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cristina IvanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Caris Life Science, Irving, TX 75039, USA.
Mark S KimDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Thanh Chung VuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pahul HanjraDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston, Houston, TX 77030, USA.
Sangbae KimHuman Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Adrian Lankenau AhumadaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Weichem WuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sanghoon LeeDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anna SzymanowskaDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hulya OztatliciDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Histology and Embryology, Gaziantep University, Gaziantep 27310, Turkey.
Marcos R EstecioDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ju-Seog LeeDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abhinav K JainDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nidhi SahniDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John P HaganDepartment of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Stephen BaylinJohns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
Jinsong LiuDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gabriel Lopez-BeresteinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sunila PradeepDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: spradeep@mcw.edu.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.

Funding

Harnessing the power of exosomes for non-coding RNA deliveryR35CA209904 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2023
$5.0M
NCI NIH HHS R35 CA209904
6 · The paper itself

Abstract

Despite the clinical use of anti-vascular endothelial growth factor (VEGF) antibodies (AVAs) in cancer therapy, resistance frequently develops, leading to disease progression. To address this, we identify a previously unknown role for breast cancer type 1 susceptibility protein (BRCA1)-associated RING domain 1 (BARD1) in modulating AVA sensitivity. Epigenetic modulation-via global and targeted DNA methylation-reveals BARD1 as a key regulator of angiogenesis. Sequential treatment with azacytidine overcomes AVA resistance in vivo. To enable precise epigenetic reactivation, we develop a liposomal CRISPR-deactivated Cas9 (dCas9)-TET1 system guided by BARD1-targeting single-guide RNAs (sgRNAs). This platform achieves CpG-specific demethylation of the BARD1 promoter, restores expression, and enhances AVA response. Additionally, BARD1 restoration, through either dCas9-TET1 or small interfering RNA (siRNA), significantly reduces tumor growth in combination with AVA in ovarian cancer models. These findings uncover a previously unrecognized function of BARD1 in tumor angiogenesis and demonstrate the potential of gene-specific epigenetic targeting to overcome AVA resistance.

Indexed as

Epigenesis, GeneticOvarian NeoplasmsTumor Suppressor ProteinsUbiquitin-Protein LigasesVascular Endothelial Growth Factor AAnimalsCell Line, TumorCRISPR-Cas SystemsDNA MethylationDrug Resistance, NeoplasmFemaleHumansMiceMixed Function OxygenasesNeovascularization, PathologicPromoter Regions, GeneticBARD1 protein, humanMixed Function OxygenasesProto-Oncogene ProteinsTET1 protein, humanTumor Suppressor ProteinsUbiquitin-Protein LigasesVascular Endothelial Growth Factor Aanti-VEGF antibody therapyAVA resistanceBARD1bevacizumabepigenetic editingepigenetic therapyovarian cancer

Identifiers

PMID40907495
PMCPMC12490209

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.